Sodium Hydroxide → HCID 87263219, Verbindung
Reaktionsgleichung
[F:1][C:2]([F:51])([F:50])[C:3]1[CH:4]=[C:5]([CH:43]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:45]=1)[CH2:6][N:7]([CH:23]([C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:26]=1[N:35]([CH2:39][CH:40]1[CH2:42][CH2:41]1)[CH2:36][CH2:37][CH3:38])[CH3:24])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20]CC)=[O:19])=[CH:10][N:9]=1.[OH-].[Na+]>C(O)C>[F:49][C:46]([F:47])([F:48])[C:44]1[CH:43]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:50])[F:51])[CH:45]=1)[CH2:6][N:7]([CH:23]([C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:26]=1[N:35]([CH2:39][CH:40]1[CH2:41][CH2:42]1)[CH2:36][CH2:37][CH3:38])[CH3:24])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[CH:12][N:13]=1Komponenten
4
Edukt 2
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Versuchsvorschrift
1-[2-(Cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethanol (500 mg) is dissolved in methylene chloride (5 ml) and thereto is added thionyl chloride (133 μl) under ice-cooling and the mixture is stirred at room temperature for 15 minutes. To the reaction solution are added methylene chloride and a saturated aqueous sodium bicarbonate solution, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue and ethyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate (749 mg) are dissolved in N,N-dimethylformamide (5 ml) and thereto is added sodium hydride (62%) (64 mg) under ice-cooling and the mixture is stirred for 1 hour. Thereto are added water and ethyl acetate, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:14:1) to give ethyl 4-[2-((3,5-bis-trifluoromethyl-benzyl)-{1-[2-(cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethyl}-amino)-pyrimidin-5-yloxy]-butyrate (144 mg) as a crude product. The resulting ester is dissolved in ethanol (2 ml) and thereto is added a 2N-aqueous sodium hydroxide solution (500 μl) and the mixture is stirred at room temperature for 2 hours and concentrated under reduced pressure. To the residue is added ethyl acetate and a dilute hydrochloric acid and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (chloroform:methanol=1:0→24:1) to give 4-[2-((3,5-bis-trifluoromethyl-benzyl)-{1-[2-(cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethyl}-amino)-pyrimidin-5-yloxy]-butyric acid (11 mg). MS (m/z): 707 [M+H]+